Unit dose capsules and dry powder inhaler

ABSTRACT

Described is a dry powder inhaler comprising an intake section; a mixing section, and a mouthpiece.

CROSS REFERENCE TO RELATED APPLICATIONS

The present application is a continuation of U.S. patent applicationSer. No. 13/408,896 filed on Feb. 29, 2012, which is a continuation ofU.S. patent application Ser. No. 11/949,707 filed on Dec. 3, 2007, whichis a divisional of U.S. patent application Ser. No. 09/621,092 filed onJul. 21, 2000, which claims the benefit under 35 U.S.C. §119(e) of U.S.Provisional Patent Applications Nos. 60/145,464 filed Jul. 23, 1999 and60/206,123 filed May 22, 2000, all of which are incorporated byreference herein in their entirety.

FIELD OF THE INVENTION

The present invention is in the field of inhalers.

BACKGROUND OF THE INVENTION

In the early 1970's it was found that certain medicines could beadministered in dry-powder form directly to the lungs by inhalationthrough the mouth or inspiration through the nose. This process allowsthe medicine to bypass the digestive system, and may, in certain cases,allow smaller does to be used to achieve the same results or orallyingested or injected medicines. In some cases, it provides a deliverytechnique that reduces side effects for medicines taken by othermedicines.

Inhaler devices typically deliver their medicinal in a liquid mist or apowder mist. The liquid mist is typically created by achlorofluorocarbon propellant. However, with the ban onchlorofluorocarbons by the Montreal protocol, interest has turned to drypowder inhalers.

For a dry powder inhaler to work effectively, it must deliver fineparticles of medicinal powder that do not agglomerate, and do not end upstriking, and being absorbed by the patient's mouth or upperoropharyngeal region. Air flow must therefore not be too fast.Furthermore, it should not be difficult for a patient to load withmedicine or to use with the proper technique. Current dry particleinhalers fail in one or more of these important criteria.

SUMMARY OF THE INVENTION

Described is a dry powder inhaler comprising an intake section; a mixingsection, and a mouthpiece. The mouthpiece is connected by a swivel jointto the mixing section, and may swivel back onto the intake section andbe enclosed by a cover. The intake chamber comprises a special pistonwith a tapered piston rod and spring, and one or more bleed-throughorifices to modulate the flow of air through the device. The intakechamber further optionally comprises a feedback module to generate atone indicating to the user when the proper rate of airflow has beenachieved. The mixing section holds a capsule with holes containing a drypowder medicament, and the cover only can open when the mouthpiece is ata certain angle to the intake section. The mixing section further opensand closes the capsule when the intake section is at a certain angle tothe mouthpiece. The mixing section is a Venturi chamber configured byprotrusions or spirals to impart a cyclonic flow to air passing throughthe mixing chamber. The mouthpiece includes a tongue depressor, and aprotrusion to contact the lips of the user to tell the user that the DPIis in the correct position. An optional storage section, with a cover,holds additional capsules. The cover for the mouthpiece, and the coverfor the storage section may both be transparent magnifying lenses.

The capsules may be two-part capsules where each portion has apertureswhich correspond to apertures in the other half when each half ispartially fitted to the other half, and fully fitted to the other half.All the apertures may be closed when the two halves are rotated aroundtheir longitudinal axes with respect to each other. Each capsule mayhave a unique key on each half that only fits with a particular inhaler.

Therefore it is an object of the invention to provide a dry particleinhaler that can fold into a compact form.

Therefore it is an object of the invention to provide a dry particleinhaler that can be loaded with medicament easily.

Therefore it is an object of the invention to provide a dry particleinhaler where the small writing on a capsule of medicament can be easilyread.

Therefore it is an object of the invention to provide a dry particleinhaler where a capsule containing medicament can only be inserted whena person unfolds the inhaler for use.

Therefore it is an object of the invention to provide a dry particleinhaler where the air flow through the device is regulated.

Therefore it is an object of the invention to provide a dry particleinhaler to provide a means for indicating to the user when the air flowis at the correct rate.

Therefore it is an object of the invention to provide a dry particleinhaler where particles of drug are dispersed finely.

These and other objects of the invention will be readily apparent upon areading of the present specification, claims and drawings.

BRIEF DESCRIPTION OF THE SEVERAL VIEWS OF THE DRAWINGS

FIG. 1 is a schematic view of the dry particle inhaler described herein.

FIG. 2 is schematic view of the mouthpiece cover.

FIG. 3 is schematic view showing the angle between the intake sectionand the mouthpiece.

FIG. 4 is a schematic view of the dry particle inhaler, showing thestorage section.

FIG. 5 is a schematic view of the intake section of the dry particleinhaler, showing the flow regulator and the feedback module.

FIG. 6 is a schematic view of the mixing section.

FIG. 7 is a schematic view of a capsule to hold medicament.

FIG. 8 is a schematic view of the mouthpiece.

FIG. 9 is a perspective view of a specific embodiment of the dryparticle inhaler in the closed position, with a capsule inserted intothe mixing section, and extra capsules stored in the storage section.

FIG. 10 is a perspective view of a specific embodiment of the dryparticle inhaler showing a capsule being loaded in to the mixingsection.

FIG. 11 is a perspective view of a specific embodiment of the dryparticle inhaler showing a capsule inserted into the mixing section, andthe mouthpiece extended for use.

FIGS. 12,13,14, and 15 follow each other in temporal sequence.

FIG. 12 is a perspective view of a specific embodiment of the dryparticle inhaler showing a closed mouthpiece cover.

FIG. 13 is a perspective view of a specific embodiment of the dryparticle inhaler showing an open mouthpiece cover.

FIG. 14 is a perspective view of a specific embodiment of the dryparticle inhaler showing an open mouthpiece cover, an open mixingsection cover, and a capsule about to be inserted into the mixingsection.

FIG. 15 is a perspective view of a specific embodiment of the dryparticle inhaler showing the mouthpiece extended for use.

FIG. 16 is a view of a pneumatic circuit, where air flows (fluid flows)are represented by their electrical equivalents.

FIG. 17 is a schematic view of the dry particle inhaler.

FIG. 18 is a cutaway view of a capsule and a portion of the mixingsection.

FIG. 19 is a cutaway view of half of a capsule, showing a cone in theinterior and a secondary hole with a chamfered, or beveled, edge.

TABLE OF REFERENCE NUMBERS

10 dry powder inhaler device 20 intake section 30 mixing section 40mouthpiece 50 air passage through dry powder inhaler device 60longitudinal axis of intake section 70 longitudinal axis of mouthpiecesection 80 swivel joint connecting mouthpiece and mixing section 90cover for mouthpiece 100 protrusions on mouthpiece cover 110 depressionson dry particle inhaler cover to mate with protrusions on mouthpiececover 120 tongue depressor on mouthpiece 130 protrusion on surface ofmouthpiece to contact lips of device user 135 opening of mouthpiece tobe fitted into user's mouth 140 intake port 150 flow regulator 160 bleedorifice 170 piston 180 piston head 190 piston rod 200 proximal portionof piston rod 210 distal portion of piston rod 220 spring 230 innerwalls of intake section inner chamber 240 feedback module 250 mechanicalfasteners in storage section 260 holder in mixing section for capsule270 Venturi chamber 280 spiral shape or protrusions to impart cyclonicflow to air 290 cover for mixing chamber 291 interior of mixing section292 air flow entrance to mixing section 294 air flow exit from mixingsection 296 latch mechanism for mixing section cover 298 interior wallof mixing section 300 capsule 310 first tube 320 open end of first tube330 closed end of first tube 340 long axis of first tube 350 protrusionon first tube 360 keying surface on first tube 370 secondary holes infirst tube 372 chamfered edge of secondary hole 375 cone in interior offirst tube 380 second tube 390 open end of second tube 400 closed end ofsecond tube 410 long axis of second tube 420 protrusion on second tube430 keying surface on second tube 440 secondary holes in second tube 445cone in interior of second tube 450 hand of user 460 air flow direction470 storage section 480 storage section cover

DETAILED DESCRIPTION OF THE INVENTION

FIG. 1 is a schematic drawing of the dry powder inhaler (10) describedherein. It comprises an intake section (20), a mixing section (30) and amouthpiece (40). An air passage (50) goes through the intake section(20), a mixing section (30) and a mouthpiece (40). A swivel joint (80)connects the mouthpiece (40) to the mixing section (30). The mixingsection (20) has a cover (290) which may be a transparent magnifyinglens.

Arrow (460) shows the direction of air flow through the air passage (50)through the dry powder inhaler (10).

FIG. 2 shows the mouthpiece cover (90) in the closed position over thedry particle inhaler (10). Protrusions (100) on the mouthpiece cover(90) mate with grooves or depressions (110) on the dry particle inhaler(10), to join the mouthpiece cover (90) to the dry particle inhaler(10).

FIG. 3 is a schematic of the showing the mouthpiece (40) and the intakesection (20) as represented by the longitudinal axis of the mouthpiece(70) and the longitudinal axis of the intake section (60). The swiveljoint (80) connecting the mouthpiece (40) to the intake section (20) atthe mixing section (30) may be regarded as the vertex of the angle. Theimportance of the angle (here called theta) between these twolongitudinal axes will be further explained.

FIG. 4 shows the dry particle inhaler (10) with a storage section (470).Indicated as being inside the storage section (470) are mechanicalfasteners (250) which operate to hold medicament capsules (300) (notshown in this Figure) in the storage section. In this embodiment, thestorage section (470) is shown as appended to the intake section (20).The storage section has a cover (480) which may be a transparentmagnifying lens, to allow the user to easily read writing on medicamentcapsules stored therein. The storage section cover (480) may swiveloutward, or slide open on a track (not shown), or open by a variety ofmechanisms known to those of skill in the art.

FIG. 5 shows the intake section (20) of the dry particle inhaler (10).The direction of air flow is shown by the arrow (460). Air is admittedthrough an intake port (140) and one or more bleed orifices (160) [Thebleed orifices may also be styled as secondary ambient air intakeports].

The piston (170) normally covers the intake port (140). When the user(not shown) inspires, the piston head (180) is drawn backwards, at asteady rate modulated by the spring (220). The spring (220) is fixed tothe piston (170) and the inner wall (230) of the intake section chamber.Thus the rate of air flow is controlled. The air flow is furthercontrolled by the tapering of the piston rod (190), past which the airflows. For further control of the air flow, a second spring (not shown)may also control the rate of movement of the piston (170).

The piston (170) and spring (220) combination allow the user (not shown)to generate a vacuum in his lungs before the intake port (140) opens.

Thus, by the time enough vacuum is generated to open the intake port(140), there will be sufficient air flow at a sufficient rate in the dryparticle inhaler (10) to draw most of the medicament in the capsule (notshown) out of the inhaler into the proper place in the lungs of theuser.

A feedback module (240) generates a signal to the user (not shown),which tells the user whether he is inspiring at the correct rate. Thesignal may be an audible one, in one embodiment a tone that is at asteady pitch when air flow is at a certain steady rate. In oneembodiment of the dry particle inhaler (10), the signal is generatedmechanically, such as be a musical reed. In another embodiment of theinvention, the signal might be generated electronically, afterelectronic measurement of the air flow rate. The feedback module (240)would include a means for increasing or lessening the signal strength,or turning the signal off entirely. If the signal were generated by areed, the mechanism for turning off the signal might be covering a bleedorifice which might admit the air flow generating the signal. If thesignal were generated electronically, a simple push button or dial mightturn on and off the signal.

FIG. 6 shows a schematic of the mixing section (30) of the presentinvention. The mixing section has a cover (290), and a holder (260) fora medicament capsule (not shown). The holder (260) is a mechanism whichgrips and turns the capsule (not shown) to open and close it as thelongitudinal axis (70) of the mouthpiece is rotated about the swiveljoint (80) relative to the longitudinal axis (60) of the intake section.Such a mechanism may be straightforward: in a simplest embodiment, boththe top and bottom halves (not shown) of the capsule could be fixed totheir respective holders (260).

The Venturi chamber (270) speeds the flow of air near the capsule (notshown). Air flows in at (292), and out through (294). In one embodiment,air flows both through and around a capsule (not shown) holding a drypowder medicament. The special shape of the Venturi chamber (270), whichfurther includes protrusions or spiral shapes (280), imparts a cyclonicflow to the air passing through the mixing section (30).

This helps to de-agglomerate particles of dry powder. The spiral shapeof the interior of the mixing section (291) can be two separate spirals,in one embodiment of the invention. Mixing section (30) thereforeprovides the means whereby air flow is speeded up to suspend dryparticles in air and de-agglomerate them, and then slow the air flowsomewhat while the particles are still suspended in air. The cover (290)for the mixing section (30) may be a transparent magnifying lens, sothat any writing on the capsule (not shown) may be read easily.

In one embodiment of the dry particle inhaler (10), the cover (290) ofthe mixing section may not be opened unless the longitudinal axis (70)of the mouthpiece forms a certain angle with the longitudinal axis (60)of the intake section, with the vertex of the angle being the swiveljoint (80) connecting the mouthpiece (40) and the mixing section (30).The latch mechanism (296) for the cover (290) of the mixing section canaccomplish this, by any of several mechanical means known to those ofordinary skill in the art. In the simplest embodiment, a catchment (notshown) in the cover (290) for the mixing chamber would be engaged by aslip ring (not shown) on the mixing section which was only a certainnumber of degrees of a circle.

When the mouthpiece (40) were rotated enough relative to the intakesection (20), the slip ring (not shown) would no longer engage thecatchment (not shown). In one embodiment, the user could open the cover(290) when the angle were between approximately ninety and one-hundredand eighty degrees.

FIG. 7 shows a medicament capsule (300) for use with an inhaler, be it adry powder inhaler (10), or a liquid mist inhaler. The capsule (300) hastwo halves which fit together, here styled a first tube (310) and asecond tube (380). Each tube has an open end (320,390), and a closed end(330,400). Each tube also has a long axis (340,410). In addition, eachtube has a number of secondary holes (370,440). The first tube (310)fits inside the second tube (380) snugly. A protrusion (350) on theouter surface of the first tube (310) can slide past a correspondingprotrusion (420) on the inner surface of the second tube (380). Thislocks the first tube (310) to the second tube (380). Therefore the firsttube (310) and the second tube (380) have both an unlocked and a lockedposition. In the unlocked position, at least one secondary hole (370) inthe first tube aligns with at least one secondary hole (440) in thesecond tube. This permits introduction of a medicament (not shown) intothe capsule through the aligned secondary holes (370,440).

The first tube (310) may then be locked to the second tube (380). When auser (not shown) is ready to use a capsule (300), he simply places it inthe holder (260) in the mixing section (30), and closes the cover (290).When the holder (260) rotates the first tube (310) around its long axis(340) relative to the second tube (380) and its long axis (410) (theaxes are now coincident), that causes at least two secondary holes (370)in the first tube to align with at least two secondary holes (440) inthe second tube. Air can now pass in, through, and out of the capsule(300), releasing the medicament contained therein. In one embodiment ofthe inhaler, the capsule (300) might open when the angle between thelongitudinal axis (70) of the mouthpiece section, the vertex of theswivel joint (80), and the longitudinal axis (70) of the mouthpiecesection were between one hundred and seventy and one-hundred and eightydegrees. This rotation of the mouthpiece (40) relative to the intakesection (20) would cause a corresponding rotation of the first tube(310) about its long axis (340) relative to the second tube (380) andits long axis (410).

In one embodiment of the invention, several protrusions on the surfacesof the first tube or the second tube might provide a variety of lockingpositions. Similarly, a variety of secondary holes in the first andsecond tubes might provide a variety of rotational positions aligning ornot aligning secondary holes on the first and second tubes.

The capsules described herein permit the introduction of liquid or gelmedicament which can be dried in the capsule, creating a powder. Thispermits the accurate production of very small amounts of powderedmedicament in a capsule, since it can be formed from a larger volume ofaccurately metered liquid or gel medicament. This permits very accuratemicrodosing. In addition, chemical reactions and drug mixtures may bemade directly in the capsules described herein, then the resultingformulation dried.

In one embodiment of the capsule (300), one or more of the secondaryholes (370,440) used to admit air to the capsule is oval-shaped(elliptical). In one embodiment of the invention, the ratio of the longaxis of the ellipse to the shorter axis may be between 1:1 and 3:1, andmay be 2:1.

This ratio may be called a vertical aspect ratio. In one embodiment ofthe invention, the intersection of the surface defining one or more ofthe secondary holes (370,440) and the surface defining the interior ofthe capsule (300) meet in a chamfered, or beveled, edge. This chamferededge creates a vortex when air flows through the secondary holes(370,440).

Each capsule (300) also has a keying surface (or fastening mechanism) onthe closed end (330) of the first tube and the closed end (400) of thesecond tube comprising the capsule. The keying surface (360) on thefirst tube may be different from the keying surface (430) on the secondtube.

That permits easy tactile and visual identification of the orientationof the capsule. It also permits a system where each drug formulation ina capsule (300) corresponds to a dry particle inhaler (10), so userscannot mix up drugs. In one embodiment of the invention, the keyingsurface (360) of the first tube mates with a keying surface (430) of adifferent second tube, or the mechanical fasteners (250) of the storagesection (470). This permits easy storage of the capsules (300) in thestorage section (470).

FIG. 18 shows a medicament capsule (300), with a keying surface (360) onthe first tube and a keying surface (430) on the second tube. It alsoshows a cutaway view of the mixing section (30) and the air flowentrance (292) to the mixing section and the air flow exit (294) to themixing section.

A spiral shape (280) is given to the interior walls (298) of the mixingsection, to impart a cyclonic flow to air passing through. The air flowentrance (292) and air flow exit (294) in this embodiment are tangentialto the imaginary tube we might call the mixing section interior (291).That is to say, if a radius were drawn perpendicular to the long axis ofthe tube, and a tangent line were drawn to the circle perpendicular tothe radius, the air flow would exit the mixing section along thattangent line. The tangential air flow exit (294) increases the velocityof the air flow, and thus helps disperse the medicament particles. Ascan be seen from FIG. 18, the mixing section interior (291) is sized toaccommodate a medicament capsule (300). Keying mechanisms (360,430) areshaped to mate with holder (260) in the mixing section. Capsulesaccording to the present invention may have a number of shapes,including ovoid and rectangular shapes. A variety of shapes ofprotrusions and slots may also be employed as keying surfaces. Forinstance, a keying surface might be a rectangular block, and a capsuleholder might have a rectangular orifice. Alternatively, a keying surfacemight be triangular, hexagonal, Z-shaped, C-shaped, etc., and the holderwould have the correspondingly shaped aperture.

FIG. 18 also shows one embodiment of the capsule (300) where a cone(375) is located in the interior of the first tube, and a cone (445) islocated in the interior of the second tube. These cones (375,445) causethe air flow within the capsule to be cyclonic, aiding in mixing themedicament particles with the air. A cone is shown herein, but othercyclone-creating structures are contemplated by the present invention.

FIG. 8 shows the mouthpiece (40) of the dry particle inhaler (10).

It has a protrusion (130) on its surface to contact the lips of a user(not shown). This helps the user place the mouthpiece correctly in hismouth.

The mouthpiece (40) also includes a tongue depressor (120), which mayhave a bulbous shape. The mouthpiece (40) is long enough that it fitsapproximately midway into the user's mouth (not shown). This permitsgreater delivery of medicament to the lungs, and less delivery to theoral cavity. The mouthpiece (40) has a particular aspect ratio of itsinner channel (50) (see FIG. 17). This slows the air passing through thechannel so that the air borne particulates do not end up striking theback of the user's throat.

However, the air is not slowed so much that the particulates settle outof the air flow.

FIG. 9, FIG. 10, and FIG. 11 show one specific embodiment of the dryparticle inhaler (10). In FIG. 9, the cover (90) of the mouthpiece isclosed, and several capsule (300) are in the storage section (470). InFIG. 10, the mouthpiece (40) has been rotated relative to the intakesection (20). The longitudinal axis (60) [not shown] of the intakesection here makes an approximately ninety degree angle with thelongitudinal axis (70) of the mouthpiece section. This permits the cover(290) for the mixing section to be opened. A medicament capsule (300)taken from the storage section (470) is about to be inserted into themixing section (30). In FIG. 11, the mouthpiece (40) has been rotated toa fully extended position, the cover (290) for the mixing section hasbeen closed, and the dry particle inhaler 910) is ready for use. In oneembodiment of the dry particle inhaler (10), when the dry particleinhaler is in the closed position (FIG. 9), the interior of the intakesection (20) would be isolated from the outside air, but the mouthpiece(40) interior and the mixing section interior (291) would not be,permitting them to dry out after being exposed to the humid breath of auser.

FIG. 12, FIG. 13, FIG. 14, and FIG. 15 show a temporal sequence where acapsule (300) of medicament is loaded into the mixing section (30) of adry particle inhaler (10), and the mouthpiece (40) is extended for use.The dry particle inhaler (10) described herein can also be used fornasal delivery of medicaments. A small tube (not shown) can be fitted tothe end of the mouthpiece (40), and the other end of the tube insertedinto the nostril. Alternatively, the mouthpiece (40) may be replaced bya nosepiece (not shown), whose free end is sized to be inserted into anostril of a user. In another embodiment, a device such as a bellows ora syringe is used to force air through the dry particle inhaler (10)into a nosepiece inserted into the nostril of a user (not shown).

FIG. 16 shows the fluid (air) flow of the dry particle inhaler (10)modeled as the equivalent electrical circuit. This is styled a“pneumatic resistance circuit”.

FIG. 17 shows a schematic view of the dry particle inhaler (10). The airpassage (50) through the dry particle inhaler widens as it goes throughthe mouthpiece (40) along the direction of the air flow (460). Theopening (135) of the mouthpiece to be inserted into the mouth of theuser may be roughly ellipsoid, or oval, and thus have a major axis and aminor axis. The ratio of these two may be called the horizontal aspectratio. In one embodiment of the invention, the horizontal aspect ratiois between 2:1 and 4:1. In one embodiment of the dry particle inhaler(10), the horizontal aspect ratio is 3:1. Shaping the opening (135) inthis manner keeps the drug particles collimated, maintains the optimalvelocity of the particles in the air stream, and is oriented to thenatural horizontal aspect ratio of the oropharyngeal region of themouth. In one embodiment of the invention, the outline of the opening(135) resembles a bean.

The dry particle inhaler described herein may be used with medicamentparticles of low, medium, and high shear forces.

The dry particle inhaler and capsules described herein may be made witha variety of suitable materials known to those skilled in the art, suchas metal, glass, rubber, and plastic.

While the invention has been described with reference to particularembodiments, those skilled in the art will be able to make variousmodifications without departing from the spirit and scope thereof.

We claim:
 1. A joint attached to a mouthpiece and configured to move acartridge keying surface.
 2. The joint of claim 1, wherein the cartridgekeying surface is a rectangular orifice.
 3. The joint of claim 1,wherein the cartridge keying surface is configured to engage with akeying surface on a lower half of a cartridge,
 4. The joint of claim 3,wherein the cartridge keying surface is configured to move the lowerhalf of the cartridge relative to an upper half of the cartridge.
 5. Thejoint of claim 1, wherein the joint is located within a housing.
 6. Thejoint of claim 3, wherein the cartridge includes a medicament.
 7. Thejoint of claim 6, wherein the medicament comprises a dry powder.
 8. Thejoint of claim 7, wherein the cartridge includes protrusions on asurface of the upper half, the lower half, or a combination thereof,thereby providing one or more locking positions.
 9. The joint of claim7, wherein the lower half of the cartridge is fixed to the keyingsurface and the upper half of the cartridge is fixed to a second keyingsurface.
 10. A cartridge for a dry powder inhaler, the cartridgecomprising: an upper half and a bottom half, wherein portions of theupper half and the bottom half are configured to align and form an airinlet including a ratio of long axis to short axis of between 1:1 and3:1.
 11. The cartridge of claim 10, wherein the bottom half has arectangular cross-sectional shape.
 12. The cartridge of claim 10,wherein the bottom half has a circular cross-sectional shape.
 13. Thecartridge of claim 10, wherein the top half and the bottom half can moverelative to each other.
 14. The cartridge of claim 13, wherein the tophalf and the bottom half can move between a locked position and anunlocked position.
 15. The cartridge of claim 13, wherein when the tophalf and the bottom half are in a locked position, the interior of thecartridge is isolated from outside air.
 16. The cartridge of claim 10,wherein the air inlet has an elliptical shape.
 17. The cartridge ofclaim 10, wherein the elliptical shape has a ratio of long axis to shortaxis of about 2:1.
 18. The cartridge of claim 10, wherein the air inlethas chamfered edges.
 19. The cartridge of claim 10, wherein thecartridge includes a medicament.
 20. The cartridge of claim 19, whereinthe medicament is a dry powder.